U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H31Cl2NO3
Molecular Weight 440.403
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRAMUSTINE

SMILES

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])C=C(OC(=O)N(CCCl)CCCl)C=C4

InChI

InChIKey=FRPJXPJMRWBBIH-RBRWEJTLSA-N
InChI=1S/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018045s023lbl.pdf

Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors. Used for the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

CNS Activity

Originator

Approval Year

1981
138
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 4.5 µM [IC50]
Modulator
828
Agonist
2678
Microtubule-associated protein 1A
5
Target ID: P78559
Gene ID: 4130.0
Gene Symbol: MAP1A
Target Organism: Homo sapiens (Human)
Antagonist
2778
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8429
Emcyt

Approved Use

EMCYT Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Launch Date

1991
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
362 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.88 μg × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
972 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16568471
280 mg 3 times / day multiple, oral
dose: 280 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ESTRAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.6 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/7736407
ESTRAMUSTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
DLT: Malaise and fatigue, Hypotension...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 75%)
Hypotension (grade 3, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
2500 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 2500 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2500 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
DLT: Malaise and fatigue...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 40%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
AEs

AEs

AESignificanceDosePopulation
Hypotension grade 3, 25%
DLT
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
Malaise and fatigue grade 3, 75%
DLT
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
Malaise and fatigue grade 3, 40%
DLT
2500 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 2500 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2500 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4868
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4868
ChemicalBook
CB9127416
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9127416
MolPort
MolPort-006-114-857
https://www.molport.com/shop/molecule-link/MolPort-006-114-857
ZINC
ZINC000004099032
http://zinc15.docking.org/substances/ZINC000004099032
eMolecules
30151822
https://www.emolecules.com/cgi-bin/more?vid=30151822
PubMed

PubMed

TitleDatePubMed
Progressing prostate carcinoma.
2001
Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2).
2001 Apr 15
Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.
2001 Feb
Current status of cytotoxic chemotherapy in hormone refractory prostate cancer.
2001 Feb
Estramustine-related hypocalcemia in patients with prostate carcinoma and osteoblastic metastases.
2001 Jul
Paclitaxel and docetaxel in prostate cancer.
2001 Jun
The bleb formation of the extracellular pseudopodia; early evidence of microtubule depolymerization by estramustine phosphate in glioma cell; in vitro study.
2001 Mar
A phase II trial of estramustine and etoposide in hormone refractory prostate cancer: A Southwest Oncology Group trial (SWOG 9407).
2001 Mar 1
Distribution of estramustine-binding protein during postnatal development of rat brain.
2001 May
[Chemotherapy of prostate cancer: potential role of docetaxel].
2001 Nov-Dec
Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes.
2001 Sep
Combination therapy in hormone-refractory prostate cancer.
2001 Sep
Controversies in chemotherapy of prostate cancer.
2002
[Second cancer after starting treatment for prostate cancer].
2002 Aug
Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
2002 Aug
Hypertriglyceridemia and pancreatitis associated with estramustine phosphate.
2002 Aug
[Therapy for hormone-refractory prostate cancer].
2002 Dec
An active regimen of weekly paclitaxel and estramustine in metastatic androgen-independent prostate cancer.
2002 Dec
Combination chemotherapy with paclitaxel, estramustine and carboplatin for hormone refractory prostate cancer.
2002 Dec
The flare in alkaline phosphatase activity post-orchidectomy predicts which patient may benefit from early chemotherapy in metastatic prostate cancer.
2002 Feb 1
Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
2002 Jan
The antimicrotubule drug estramustine but not irradiation induces apoptosis in malignant glioma involving AKT and caspase pathways.
2002 Jan
Docetaxel in the integrated management of prostate cancer. Current applications and future promise.
2002 Jun
Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer.
2002 Jun
Acute estramustine-induced hypocalcemia unmasking severe vitamin D deficiency.
2002 Jun 1
High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.
2002 Jun 5
A phase II Hoosier Oncology Group study of vinorelbine and estramustine phosphate in hormone-refractory prostate cancer.
2002 Mar
Estramustine phosphate enhances the effects of hyperthermia and induces the small heat shock protein HSP27 in the human prostate carcinoma cell line PC-3.
2002 May
Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer.
2002 Nov
Drug resistance in prostate cancer cell lines is influenced by androgen dependence and p53 status.
2002 Oct
Combined anti-microtubule therapy: a phase II study of weekly docetaxel plus estramustine in patients with metastatic breast cancer.
2002 Oct
Chemotherapy for prostate cancer.
2002 Sep
Weekly epirubicin in patients with hormone-resistant prostate cancer.
2002 Sep 23
[Prostatic cancer in the young adult].
2003 Apr
Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer.
2003 Apr
Docetaxel (taxotere) in the treatment of prostate cancer.
2003 Jun
[Malignant priapism as a sign of a recurrent prostate cancer. Differential diagnosis of induratio penis plastica].
2003 Jun
Chemotherapy of prostate cancer: present and future.
2003 Jun
Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer.
2003 Mar 1
Physician attitudes toward cytotoxic chemotherapy use in patients with advanced prostate carcinoma.
2003 May 1
Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells.
2003 May 16
Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints.
2003 May-Jun
High-risk localized prostate cancer: primary surgery and adjuvant therapy.
2003 May-Jun
Patents

Patents

05036062
5
JP2002511777A
414
JP2003529540A
49
JP2005519871A
28
JP2005520795A
24
JP2007538099A
18
JP2009513567A
65
JP2011522802A
30
JP2011524416A
138
JPS61189214A
6

Sample Use Guides

In Vivo Use Guide
The recommended daily dose is 14 mg per kg of body weight (ie, one 140 mg capsule for each 10 kg or 22 lb of body weight), given in 3 or 4 divided doses. Most patients in studies in the United States have been treated at a dosage range of 10 to 16 mg per kg per day.
Route of Administration: Oral
In Vitro Use Guide
Estramustine inhibited human endothelial cell proliferation with an IC50 of 4.5 uM and was active at 10-33% of the maximum tolerated dose (MTD) from clinical schedules
Name Type Language
ESTRAMUSTINE
INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
RO-22-2296/000
Code English
RO 22-2296/000
Code English
NSC-89201
Code English
Estramustine [WHO-DD]
Common Name English
estramustine [INN]
Common Name English
RO-222296000
Code English
RO-22-2296000
Code English
ESTRA-1,3,5(10)-TRIENE-3,17-DIOL, 3-(BIS(2-CHLOROETHYL)CARBAMATE), (17B)-
Common Name English
ESTRAMUSTINE [USAN]
Common Name English
ESTRAMUSTINE [MI]
Common Name English
ESTRAMUSTINE [VANDF]
Common Name English
Estradiol 3-[bis(2-chloroethyl)carbamate]
Common Name English
Classification Tree Code System Code
NDF-RT N0000007246
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
WHO-ATC L01XX11
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000175558
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
LIVERTOX 373
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000007246
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NCI_THESAURUS C697
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NCI_THESAURUS C25974
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NDF-RT N0000007659
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
WHO-VATC QL01XX11
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NDF-RT N0000000236
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
Code System Code Type Description
EVMPD
SUB07246MIG
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PRIMARY
MESH
D004961
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PRIMARY
MERCK INDEX
m5031
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PRIMARY Merck Index
WIKIPEDIA
ESTRAMUSTINE
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PRIMARY
RXCUI
4089
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PRIMARY RxNorm
CHEBI
4868
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
SMS_ID
100000082381
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PRIMARY
DRUG BANK
DB01196
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PRIMARY
EPA CompTox
DTXSID8046458
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PRIMARY
NCI_THESAURUS
C479
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PRIMARY
ChEMBL
CHEMBL1575
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PRIMARY
PUBCHEM
259331
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
FDA UNII
35LT29625A
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
ECHA (EC/EINECS)
221-076-3
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
CAS
2998-57-4
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
DRUG CENTRAL
1065
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PRIMARY
INN
2877
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PRIMARY
NSC
89201
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PRIMARY
DAILYMED
35LT29625A
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of ESTRAMUSTINE
METABOLITE (PARENT)
Structure of ESTRADIOL
PRODRUG (METABOLITE ACTIVE)
Structure of ESTRAMUSTINE PHOSPHATE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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